Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT

Research output: Contribution to journalArticlepeer-review

Standard

Adrenaline to improve survival in out-of-hospital cardiac arrest : the PARAMEDIC2 RCT. / Perkins, Gavin D; Ji, Chen; Achana, Felix; Black, John Jm; Charlton, Karl; Crawford, James; de Paeztron, Adam; Deakin, Charles; Docherty, Mark; Finn, Judith; Fothergill, Rachael T; Gates, Simon; Gunson, Imogen; Han, Kyee; Hennings, Susie; Horton, Jessica; Khan, Kamran; Lamb, Sarah; Long, John; Miller, Joshua; Moore, Fionna; Nolan, Jerry; O'Shea, Lyndsey; Petrou, Stavros; Pocock, Helen; Quinn, Tom; Rees, Nigel; Regan, Scott; Rosser, Andy; Scomparin, Charlotte; Slowther, Anne; Lall, Ranjit.

In: Health Technology Assessment, Vol. 25, No. 25, 30.04.2021, p. 1-166.

Research output: Contribution to journalArticlepeer-review

Harvard

Perkins, GD, Ji, C, Achana, F, Black, JJ, Charlton, K, Crawford, J, de Paeztron, A, Deakin, C, Docherty, M, Finn, J, Fothergill, RT, Gates, S, Gunson, I, Han, K, Hennings, S, Horton, J, Khan, K, Lamb, S, Long, J, Miller, J, Moore, F, Nolan, J, O'Shea, L, Petrou, S, Pocock, H, Quinn, T, Rees, N, Regan, S, Rosser, A, Scomparin, C, Slowther, A & Lall, R 2021, 'Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT', Health Technology Assessment, vol. 25, no. 25, pp. 1-166. https://doi.org/10.3310/hta25250

APA

Perkins, G. D., Ji, C., Achana, F., Black, J. J., Charlton, K., Crawford, J., de Paeztron, A., Deakin, C., Docherty, M., Finn, J., Fothergill, R. T., Gates, S., Gunson, I., Han, K., Hennings, S., Horton, J., Khan, K., Lamb, S., Long, J., ... Lall, R. (2021). Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT. Health Technology Assessment, 25(25), 1-166. https://doi.org/10.3310/hta25250

Vancouver

Perkins GD, Ji C, Achana F, Black JJ, Charlton K, Crawford J et al. Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT. Health Technology Assessment. 2021 Apr 30;25(25):1-166. https://doi.org/10.3310/hta25250

Author

Perkins, Gavin D ; Ji, Chen ; Achana, Felix ; Black, John Jm ; Charlton, Karl ; Crawford, James ; de Paeztron, Adam ; Deakin, Charles ; Docherty, Mark ; Finn, Judith ; Fothergill, Rachael T ; Gates, Simon ; Gunson, Imogen ; Han, Kyee ; Hennings, Susie ; Horton, Jessica ; Khan, Kamran ; Lamb, Sarah ; Long, John ; Miller, Joshua ; Moore, Fionna ; Nolan, Jerry ; O'Shea, Lyndsey ; Petrou, Stavros ; Pocock, Helen ; Quinn, Tom ; Rees, Nigel ; Regan, Scott ; Rosser, Andy ; Scomparin, Charlotte ; Slowther, Anne ; Lall, Ranjit. / Adrenaline to improve survival in out-of-hospital cardiac arrest : the PARAMEDIC2 RCT. In: Health Technology Assessment. 2021 ; Vol. 25, No. 25. pp. 1-166.

Bibtex

@article{eb6249d560da4dbe9e05c68aa7dc0eea,
title = "Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT",
abstract = "BACKGROUND: Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.OBJECTIVES: The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.DESIGN: This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices.SETTING: This trial was set in five NHS ambulance services in England and Wales.PARTICIPANTS: Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given.INTERVENTIONS: Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs.MAIN OUTCOME MEASURES: The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation.RESULTS: From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest.LIMITATIONS: The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome.CONCLUSIONS: Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS.FUTURE WORK: Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective.TRIAL REGISTRATION: Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11.FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.",
author = "Perkins, {Gavin D} and Chen Ji and Felix Achana and Black, {John Jm} and Karl Charlton and James Crawford and {de Paeztron}, Adam and Charles Deakin and Mark Docherty and Judith Finn and Fothergill, {Rachael T} and Simon Gates and Imogen Gunson and Kyee Han and Susie Hennings and Jessica Horton and Kamran Khan and Sarah Lamb and John Long and Joshua Miller and Fionna Moore and Jerry Nolan and Lyndsey O'Shea and Stavros Petrou and Helen Pocock and Tom Quinn and Nigel Rees and Scott Regan and Andy Rosser and Charlotte Scomparin and Anne Slowther and Ranjit Lall",
year = "2021",
month = apr,
day = "30",
doi = "10.3310/hta25250",
language = "English",
volume = "25",
pages = "1--166",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "NIHR Health Technology Assessment Programme",
number = "25",

}

RIS

TY - JOUR

T1 - Adrenaline to improve survival in out-of-hospital cardiac arrest

T2 - the PARAMEDIC2 RCT

AU - Perkins, Gavin D

AU - Ji, Chen

AU - Achana, Felix

AU - Black, John Jm

AU - Charlton, Karl

AU - Crawford, James

AU - de Paeztron, Adam

AU - Deakin, Charles

AU - Docherty, Mark

AU - Finn, Judith

AU - Fothergill, Rachael T

AU - Gates, Simon

AU - Gunson, Imogen

AU - Han, Kyee

AU - Hennings, Susie

AU - Horton, Jessica

AU - Khan, Kamran

AU - Lamb, Sarah

AU - Long, John

AU - Miller, Joshua

AU - Moore, Fionna

AU - Nolan, Jerry

AU - O'Shea, Lyndsey

AU - Petrou, Stavros

AU - Pocock, Helen

AU - Quinn, Tom

AU - Rees, Nigel

AU - Regan, Scott

AU - Rosser, Andy

AU - Scomparin, Charlotte

AU - Slowther, Anne

AU - Lall, Ranjit

PY - 2021/4/30

Y1 - 2021/4/30

N2 - BACKGROUND: Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.OBJECTIVES: The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.DESIGN: This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices.SETTING: This trial was set in five NHS ambulance services in England and Wales.PARTICIPANTS: Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given.INTERVENTIONS: Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs.MAIN OUTCOME MEASURES: The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation.RESULTS: From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest.LIMITATIONS: The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome.CONCLUSIONS: Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS.FUTURE WORK: Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective.TRIAL REGISTRATION: Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11.FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.

AB - BACKGROUND: Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes.OBJECTIVES: The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use.DESIGN: This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices.SETTING: This trial was set in five NHS ambulance services in England and Wales.PARTICIPANTS: Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given.INTERVENTIONS: Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs.MAIN OUTCOME MEASURES: The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation.RESULTS: From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest.LIMITATIONS: The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome.CONCLUSIONS: Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS.FUTURE WORK: Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective.TRIAL REGISTRATION: Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11.FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.

U2 - 10.3310/hta25250

DO - 10.3310/hta25250

M3 - Article

C2 - 33861194

VL - 25

SP - 1

EP - 166

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 25

ER -